Global expression profiling of RNA and small RNA from various bodily fluids and tissue biopsies has become a staple approach for the monitoring and/or discovery of RNA biomarkers in various applications, including molecular diagnostics, dose/response effects studies, toxicity studies and other related applications. Global gene expression analysis can be carried out using a variety of methods including microarray analysis, library construction, reverse transcription, amplification, transcriptome profiling, expression analysis and sequencing, including next generation sequencing.
Human blood and more particularly, plasma and serum, contain a variety of RNA molecules, which may be medically or scientifically relevant. The relative abundances of such RNA molecules can be indicative of donor health status or responses to various endogenous and exogenous stimuli. Of the RNA molecules present in human plasma and serum, a class of small non-coding, regulatory RNAs, called microRNA (miRNA), are of particular interest as biomarkers. Interest in miRNA as biomarkers is due to both their biological role in gene expression regulation and their relative stability in circulation (as compared to larger RNA molecules, which are more readily degraded).
However, miRNA is a relatively minor constituent of the human plasma and serum small RNA milieu, mostly as result of an overwhelming abundance of another short, non-coding, RNA molecule derived from the 5′ end of human RNAY4, encoded by the hY4 gene (Dhahbi et al., 2013; Brenu et al., 2014). The exact function and importance of the 5′-RNAY4 fragment has yet to be conclusively determined. Further, within the total miRNA population derived from human blood, plasma and serum, it has been found that certain miRNAs, such as miR-486-5p which has been observed to be reduced in human cancer (Song et al. 2013; Chen et al., 2015), are overrepresented.